Dataset Information

Association between Anti-Ganglionic Nicotinic Acetylcholine Receptor (gAChR) Antibodies and HLA-DRB1 Alleles in the Japanese Population.

ABSTRACT:

Background/aims

Anti-ganglionic nicotinic acetylcholine receptor (gAChR) antibodies are observed in autoimmune diseases, as well as in patients with autoimmune autonomic ganglionopathy. However, the genetic background of anti-gAChR antibodies is unclear. Here, we investigated HLA alleles in autoimmune hepatitis (AIH) patients with or without anti-gAChR antibodies.

Methodology/principal findings

Genomic DNA from 260 patients with type-1 autoimmune hepatitis (AIH) were genotyped for HLA-A, B, DRB1, and DQB1 loci. Anti-gAChR antibodies in the sera form AIH patients were measured using the luciferase immunoprecipitation system, and examined allelic association in patients with or without anti-gAChR antibodies.

Methodology/ methods

We detected anti-?3 or -?4 gAChR antibodies in 11.5% (30/260) of patients with AIH. Among AIH patients there was no significant association between HLA-A, B DQB1 alleles and the positivity for anti-gAChR antibodies. Whereas the HLA-DRB1*0403 allele showed a significantly increased frequency in AIH patients with anti-gAChR antibodies compared with those without anti-gAChR antibodies.

Conclusions/significance

The frequency of the HLA-DRB1*0403 allele differed among Japanese patients with AIH according to the presence or absence of anti-gAChR antibodies. Our findings suggest that particular HLA class II molecules might control the development of anti-gAChR antibodies in the autoimmune response to gAChR.

SUBMITTER: Maeda Y

PROVIDER: S-EPMC4726510 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Association between Anti-Ganglionic Nicotinic Acetylcholine Receptor (gAChR) Antibodies and HLA-DRB1 Alleles in the Japanese Population.

Maeda Yasuhiro Y Migita Kiyoshi K Higuchi Osamu O Mukaino Akihiro A Furukawa Hiroshi H Komori Atsumasa A Nakamura Minoru M Hashimoto Satoru S Nagaoka Shinya S Abiru Seigo S Yatsuhashi Hiroshi H Matsuo Hidenori H Kawakami Atsushi A Yasunami Michio M Nakane Shunya S

PloS one 20160125 1

<h4>Background/aims</h4>Anti-ganglionic nicotinic acetylcholine receptor (gAChR) antibodies are observed in autoimmune diseases, as well as in patients with autoimmune autonomic ganglionopathy. However, the genetic background of anti-gAChR antibodies is unclear. Here, we investigated HLA alleles in autoimmune hepatitis (AIH) patients with or without anti-gAChR antibodies.<h4>Methodology/principal findings</h4>Genomic DNA from 260 patients with type-1 autoimmune hepatitis (AIH) were genotyped for ...[more]

PMID: 26807576

Similar Datasets

Project description:Autoimmune hepatitis (AIH) is a chronic progressive liver disease. AIH is composed predominantly of type 1 in Japanese populations. The genetic and environmental factors are associated with the pathogenesis of AIH. HLA-DRB1*03:01 and *04:01 are associated with type 1 AIH in European and *04:05 in Japanese populations. Here, we conducted an HLA association study in order to find HLA alleles or haplotypes predisposing or protective for Japanese AIH.HLA-DRB1 and DQB1 genotyping of 360 type 1 AIH patients and 1026 healthy controls was performed.The predisposing association of DRB1*04:01 (P = 0.0006, corrected P [Pc] = 0.0193, odds ratio [OR] 2.97, 95% confidence interval [CI] 1.62-5.43), DRB1*04:05 (P = 1.89×10-21, Pc = 5.86×10-20, OR 3.41, 95% CI 2.65-4.38), and DQB1*04:01 (P = 4.66×10-18, Pc = 6.99×10-17, OR 3.89, 95% CI 2.84-5.33) and the protective association of DRB1*13:02 (P = 0.0003, Pc = 0.0080, OR 0.48, 95% CI 0.32-0.72) with Japanese type 1 AIH were observed. An association of the DR4/DR8 heterozygous genotype with Japanese AIH was identified for the first time (P = 3.12×10-9, OR 3.52, 95% CI 2.34-5.29). Susceptible diplotypes were DRB1*04:05-DQB1*04:01/DRB1*08:02-DQB1*03:02 (P = 0.0004, OR 24.77, 95% CI 1.45-424.31) and DRB1*04:05-DQB1*04:01/DRB1*08:03-DQB1*06:01 (P = 1.18×10-6, OR 10.64, 95% CI 3.19-35.46). Serum levels of Immunoglobulin G and Immunoglobulin M, International Autoimmune Hepatitis Group score, positive rate of anti-smooth muscle antibodies, and the rate of definite AIH were higher in AIH patients with DRB1*04:05 than without.The important roles of specific combinations of DRB1 and DQB1 alleles or haplotypes in the pathogenesis of type 1 AIH were suggested. The association of DR4/DR8 heterozygous genotype suggested the pathologic importance of trans-complementing DQ?-? heterodimer molecules encoded by DQA1 allele of one haplotype and the DQB1 allele of the other haplotype, as it was proposed in the HLA association studies of Type 1 diabetes.

Dataset Information

Association between Anti-Ganglionic Nicotinic Acetylcholine Receptor (gAChR) Antibodies and HLA-DRB1 Alleles in the Japanese Population.

Background/aims

Methodology/principal findings

Methodology/ methods

Conclusions/significance

Publications

Association between Anti-Ganglionic Nicotinic Acetylcholine Receptor (gAChR) Antibodies and HLA-DRB1 Alleles in the Japanese Population.

Similar Datasets

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